OP0041 LIFETIME MULTIMORBIDITY PROGRESSION IN RHEUMATOID ARTHRITIS: A MULTISTATE MODELLING ANALYSIS OF 20 YEAR DATA FROM THE NORFOLK ARTHRITIS REGISTER
Authors: P. Saha, J. Dainty, M. Yates, E. Kulinskaya, A. Macgregor
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The relationship between multiple long term conditions (MLTC) and rheumatoid arthritis (RA) is well known; however the trajectory of accumulation of MLTC and the factors that influence the rate of progression of MLTC following the onset of RA are yet to be fully established. The Norfolk Arthritis Register (NOAR) is a cohort study established in 1989 to record incident cases of early inflammatory arthritis, and is unique in its long follow-up period of up to 20 years. Here we examine the pattern of MLTC progression in the cohort, and apply a multistate model to examine the factors that influence MLTC progression. <h3>Objectives:</h3> Describe the patten of MLTC progression among newly diagnosed cases with RA over the disease course. Develop and apply a multistate model to examine the rate of accumulation of MLTC among people with RA following disease onset. Examine predictors that influence the rate of MLTC at different timepoints in the disease course. <h3>Methods</h3> The Norfolk Arthritis Register (NOAR) is an inception cohort of early inflammatory arthritis established in 1989, with over 4500 cases of new onset inflammatory arthritis. Cases were recruited in primary care or from hospital clinics, and inclusion criteria were age &gt;16 years with 2 swollen joints lasting ≥4 weeks. The analysis focused on 13 self-reported chronic diseases involving multiple organ systems ascertained at each follow up point over an interval of 20 years. A multistate model was constructed to examine the accumulation of the number of MLTCs over time ('states') since the onset of disease. Death was included as a separate state. Demographic data at baseline and follow up was included in the model. The multistate model was implemented in the R package <i>msm,</i> which provides longitudinal information on the transfer rates from the lower to higher levels of MLTC-M and to death. Multivariate multiple imputation (nburn=1000, 5 datasets) was used to impute missing values using R packages <i>mice</i> and <i>jomo</i>. <h3>Results</h3> The analysis is based on 4674 patients observed 2 to 15 times; this provided 33,356 records in total. The number of comorbidities increases over time from onset of RA, rho=0.299 (p-value &lt; 2.2e-16). This increase was more pronounced than the increase by age, rho=0.159 (p-value &lt; 2.2e-16), suggesting that inflammation drives number of comorbidities more than age. There were 269 unique combinations of MLTC. The most frequent single morbidities were hypertension, depression and lung disease, with frequencies 0.325, 0.320, and 0.167, respectively (0.812 total probability). The multistate model (Figure 1) considered six defined MLTC states corresponding to total number of MLTC conditions: ranging from State-1 representing RA alone to State-6 representing death. The best fitting model proved to be an additive model including the 5 predictors of gender, age of onset, BMI, smoking status and logDMARDs. Males had significantly higher hazards of accumulation of MLTCs and mortality risk. The total number of MLTCs alone were not associated with the hazard of death. Being overweight significantly increases hazards of progression from State-2 to State-3, and 3 to 4, but also did not affect hazards of death. Ex and non-smokers had significantly lower hazards of accumulation of MLTCs and death, and the number of DMARDs reduced disease progression from State-2 to State-3, and 3 to 4, but did not affect mortality. <h3>Conclusion</h3> This study provides a comprehensive long-term picture of the rate and pattern of accumulation of multimorbidity in RA over the disease course. MLTC involved most patients with RA over time. Smoking, obesity and the use of disease modifying drugs were all found to influence the rate of MLTC accumulation across a range of organ systems. The data suggest that sustained control of inflammation in RA, both through drug interventions and lifestyle management is an important part of limiting the risk of MLTC development throughout the disease course. <h3>References: NIL.</h3> <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.